Organic synthesis is established as one of the most significant tools in drug discovery and biomedical research. The development of practical, environmentally friendly chemical synthesis remains an important goal in medicinal and process chemistry, as the sustainable development of new medicines is dependent on the availability of excellent synthetic methods. Catalytic methods are highly desirable as they minimize the formation of unwanted waste byproducts, offering a more efficient alternative to classical organic reactions. This proposal describes research into new chiral Brnsted acid catalysts for alkylation reactions with trichloroacetimidate electrophiles that will provide complex heterocyclic products in an efficient, expedient manner. In Aim 1 of the proposal will investigate the reaction of trichloroacetimidate electrophiles and indoles to produce pyrroloindolines and related systems. This chemistry will then be used to facilitate an expedient synthesis of the antitumor agent neoxaline. In Aim 2 the synthesis of pyrroloindoline trichloroacetimidates will be investigated, and their reactivity with heteroatom nucleophiles will be determined. These reactions are also catalyzed with Brnsted acids. This methodology will then be used in a synthesis of kapakahine C, a second molecule with antitumor properties. In Aim 3 the pyrroloindoline imidates will be used as alkylating agents with carbon nucleophiles. This methodology will then be used in the synthesis of pestalazine A and asperazine, molecules with unusual structures. The new reactions developed in this proposal will allow medicinal and process chemists more facile access to complex high value-added organic compounds. These products will in turn be useful in the synthesis of new materials and medicines to further biomedical research.